Singlet Oxygen Induced Products of Linoleates, 10- and 12-, Can Be Potential Biomarkers for Early Detection of Type 2 Diabetes

• Published in: PloS one Vol. 8; no. 5; p. e63542
• Main Authors: Umeno, Aya, Shichiri, Mototada, Ishida, Noriko, Hashimoto, Yoshiko, Abe, Kaori, Kataoka, Masatoshi, Yoshino, Kohzoh, Hagihara, Yoshihisa, Aki, Nanako, Funaki, Makoto, Asada, Yasuhiko, Yoshida, Yasukazu
• Format: Journal Article
• Language: English
• Published: Public Library of Science 15.05.2013
• Subjects: Active oxygen; Biological markers; C-reactive protein; Glucose; Glucose tolerance test; Glycosylated hemoglobin; Insulin; Leptin; Lipid peroxidation; Prediabetic state; Type 2 diabetes; Unsaturated fatty acids
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0063542

Current diagnostic tests such as glycemic indicators have limitations for early detection of impaired glucose tolerance (IGT), which leads to diabetes. Oxidative stress induced by various oxidants in a random and destructive manner is considered to play an important role in the pathophysiology of a number of human disorders and diseases such as impaired glucose tolerance. We have developed an improved method for the measurement of in vivo lipid peroxidation, where the presence of 8-iso-prostaglandin F.sub.2[alpha] (8-iso-PGF.sub.2[alpha] ), hydroxyoctadecadienoic acids (HODEs), hydroxyeicosatetraenoic acids (HETEs), and 7-hydroxycholesterol (7-OHCh), as well as their parent molecules, linoleic acid (LA) and cholesterol (Ch), was determined by performing LC-MS/MS (for 8-iso-PGF.sub.2[alpha], HODE, and HETE) and GC-MS (for 7-OHCh, LA, and Ch) after reduction with triphenyl phosphine and saponification by potassium hydroxide. We then applied this method to volunteers (n = 57), including normal type (n = 43), "high-normal" (fasting plasma glucose, 100-109 mg/dL, n = 7), pre-diabetic type (IGT, n = 5), and diabetic type (n = 2) subjects who are diagnosed by performing oral glucose tolerance tests (OGTTs). Several biomarkers in plasma, such as insulin, leptin, adiponectin, interleukin-6, tumor necrosis factor-[alpha], high sensitivity-C-reactive protein, HbA1c, and glucose levels were measured during OGTT. We found that the fasting levels of (10- and 12-(Z,E)- HODE)/LA increased significantly with increasing levels of HbA1c and glucose during OGTT and with insulin secretion and resistance index. In conclusion, 10- and 12-(Z,E)-HODE may be prominent biomarkers for the early detection of IGT and "high-normal" type without OGTT.